ACTA ENDOCRINOLOGICA (BUC)

Context. Thyroid disorders are common in diabetics and related to severe diabetic complications. TRPV2 ion channels have crucial functions in insulin secretion and glucose metabolism which have an important role in the pathophysiology of diabetes. Also, they have a significant effect on various immunological events that are involved in the HT pathophysiology. Objective. This study aimed to investigate rs14039 and rs4792742 polymorphisms of the TRPV2 ion channels in type 2 diabetes mellitus (T2DM, n=100) Hashimoto thyroiditis (HT, n=70) and comorbid T2DM and HT (T2DM+HT, n=100) patients and control (n=100). Design. Case-control study Subject and Methods. RT-PCR genotyping was used to determine rs14039 and rs4792742 polymorphisms with DNA samples of subjects and appropriate primer and probes. Besides, required biochemical analyses were performed. Results. It was determined that the frequencies of the rs14039 GG homozygote polymorphic genotype and the G allele were significantly higher in T2DM+HT patients compared to the control (p=0.03 and p=0.01, respectively) and that especially the GG genotype increases the risk of T2DM+HT 3.046-fold (p=0.01, OR=3.046). It was detected that the GG genotype increased the risk of HT 2.54-fold (p=0.05, OR=2.541). TRPV2 rs4792742 polymorphisms reduce the risk of HT and T2DM+HT comorbidity almost by half and have a protective effect against HT and T2DM+HT. Conclusion. The rs14039 GG genotype of the TRPV2 gene significantly increases the risks of development of T2DM+HT and HT disorders, may have a significant role in the pathophysiology of these diseases, also leading to predisposition for their development. Conversely, rs4792742 polymorphic genotypes have a strong protective effect against the HT and T2DM+HT comorbidity.

Context. Chronic stress is characterized by increased release of catecholamines, glucocorticoids and other neurohumoral factors, predisposing individuals to obesity, insulin resistance and vascular disease, pathologies considered priority health problems. Study of alterations induced by stress on metabolism in association with food intake modulatory hormones (insulin, leptin and ghrelin) is mandatory. Objective. This research studied temporal course during 60 days of chronic unpredictable mild stress (CUMS) on glucose and lipids metabolism, and on the neuroendocrine system that regulates appetite-satiety balance. Materials and Methods. Wistar rats were exposed to CUMS for 20, 40 and 60 days. Corticosterone stayed high during 60 days of CUMS; after 40 days, body weight, cholesterol and triglycerides decreased and glucose intolerance was evident at day 60; insulin and ghrelin increased at 20 and 40 days, respectively; leptin decreased after day 20. Data suggest that 60 days of CUMS progressively disturb metabolism of carbohydrates and lipids as well as food intake regulatory hormones, affecting the metabolism, and can lead to the development of chronic degenerative diseases, such as cardiovascular disease, metabolic syndrome and type 2 diabetes.

Context. Oxytocin has been investigated as a potential medication for psychiatric disorders. Objective and design. This study prospectively investigates correlations between oxytocin and other neuropeptides plasma levels in patients with autism spectrum disorders (ASD) according to severity and treatment, as compared to controls. Subjects and methods. Thirty-one children (6 neurotypical as control) participated in this study. The patients were classified into mildly and severely-affected, according to Autism Diagnostic Observation Schedule (ADOS) scores. Oxytocin, orexin A and B, α-MSH, β-endorphins, neurotensin and substance P were investigated using a quantitative multiplex assay or a competitive-ELISA method. Results. Plasma oxytocin levels differed between the groups (F (2, 24) =6.48, p=0.006, η2=0.35, observed power=86%): patients with the mild ASD had higher values of plasma oxytocin than those with the severe form (average difference=74.56±20.74pg/mL, p=0.004). Conclusions. These results show a negative correlation between plasma levels of oxytocin and the severity of ASD and support the involvement of oxytocinergic mechanisms in ASD.

Objective. The aim of the study was to investigate the role of Hepatocyte Growth Factor (HGF)/c-Met pathway in testicular damage provoked by streptozotocin (STZ)- induced diabetes and the effects of insulin treatment on the HGF/c-Met pathway. Methods. Total 21 paraffin-embedded testicular tissues of control (n=7), streptozotocin (STZ)-induced diabetic (n=7) and insulin-treated diabetic (n=7) Wistar albino rats were used in this study. Testicular damage was examined histologically and by Johnsen’s score was also evaluated. Immunohistochemical stainings of HGF and c-Met were analysed by using antibodies against HGF and c-Met. Results. We found the degeneration in seminiferous tubule epithelium and disorganization of spermatogenetic cell series in testis tissues of diabetic rats. We also determined decrease both in seminiferous tubule diameter and Johnsen’s scores in diabetic group. The expressions of HGF and c-Met in seminiferous tubule epithelium and in spermatogenic cells (especially spermatocytes and spermatids) were significantly increased in diabetic rats compared to those of control. Insulin treatment significantly reduced the diabetes-induced morphological changes and HGF/c-Met over expressions in the diabetic rat testis. Conclusion. HGF/c-Met pathway might have a role in diabetes- induced testicular damage. Drugs acting on this pathway might be effective to prevent or delay the testicular damage induced by diabetes.

Background. Gangliosides are Nacetyl - neuraminic - acid containing glycosphyngolipids that modulate several\r\ncellular functions.\r\nObjective. The present study confirmed the presence of cellular gangliosides in melanocytic tumors with\r\nneuroectodermal origin. These molecules showed large quantitative and structural variability in melanocytic cells.\r\nMethods. The spectrum and levels of gangliosides were performed from 1991 until 2010, in 411 specimens of melanoma, 108 cutaneous metastases of melanoma, 206\r\nnevocellular and dysplastic nevus and 130 specimens of normal skin.\r\nResults. Melanoma showed aberrant gangliosides expression. This included overexpression of normal ganglioside\r\nconstituents (GM2, GM3, GD2, GD3), which also appear in melanocytic nevus and epidermis tissues, and expression of\r\ngangliosides (O-Acetyl-Ganglioside) not found in normal adult tissue. The ganglioside composition of\r\nmelanoma is: GM1 (1,29?0,87%), GM2 (10,32?4,11%), GM3 (22,23?11,30%), GD2 (16,03?9,13%), GD3 (39,06?14,25%), GD1a\r\n(2,16?0,77%), GD1b (1,74?1,01%), GT1b (1,82?1,11 %), GQ1b (1,34?1,07%), OAcetyl-GD3 (4,01?2,81%).\r\nConclusions. The overexpression and variability of gangliosides in melanoma and the low expression of them in normal tissue was correlated with oncogenic process and\r\nmetastatic potential.

Hypothalamic kisspeptin signaling has been recently observed to correlate with seasonal breeding in free ranging male rhesus monkeys. Recent evidence also suggests that excitatory and inhibitory amino acid neurotransmitters contribute in regulation of kisspeptin neurons. Objective. The present study was focused on analyzing the interplay of Kiss1 neurons with afferent excitatory and inhibitory signals in the brain of male rhesus monkeys during the breeding and non breeding seasons. We hypothesized that: kisspeptin stimulation may occur due to the increase in N-methyl-D,L-aspartate (NMDA) dependant excitatory inputs and decrease in inhibitory γ-aminobutyric acid (GABA) based cues during the breeding season Materials and Methods. Messenger ribonucleic acid (mRNA) was extracted from the medio basal hypothalamus (MBH) of five free ranging adult male rhesus monkeys (Macaca mulatta) during the breeding season (n=3; October; plasma testosterone levels: 26.15±2.64 nmol/L; testicular volume: 69.00 ± 0.57 ml); and the non-breeding season (n=2; July; plasma testosterone levels: 4.09±1.64 nmol/L; testicular volume: 12.88±0.31 ml). Real time polymerase chain reaction (RT-PCR) was used to quantify the levels of Kiss1, Kiss1r, NR1 and glutamic acid decarboxylase (GAD67) mRNA, relative to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Results. Significantly high (p<0.05) expression of Kiss1, Kiss1r and NR1 mRNA and low (p<0.05) expression of GAD67 mRNA in the hypothalamus were found to be in synchrony with the breeding season. Conclusion. Based on correlative gene expression changes in the adult male monkey hypothalamus we suggest that in higher primates increased kisspeptin signaling during breeding season may be entrained by an increase in NMDA excitatory inputs; while decreased kisspeptin signaling during the non-breeding season may be driven by an increase in GABA based inhibitory cues.

Introduction. Diabetic chronic kidney disease has more fatal clinical progresses and this situation can be related to volume overload, which is seen more commonly in diabetic chronic kidney disease patients than in non-diabetic chronic kidney disease patients. Therefore, we examined the effect of diabetes mellitus on volume overload in newly diagnosed stage 5 chronic kidney disease patients whose volume overloads were not showing signs of improvement from renal replacement therapy. Method. One hundred and five patients (46 diabetic, 59 non-diabetic) with end-stage chronic kidney disease, who had glomerular filtration rate (GFR) under 15 mL/min for at least three months were enrolled in this prospective study. We determined the body volume overload and configuration using a bioimpedance device. NT-proBNP levels were recorded. Results. There was a statistically significant difference between diabetic and non-diabetic groups according to overhydration (OH, p=0.003), extracellular water (ECW, p=0.045), intracellular water (ICW, p<0.001) and OH/ECW (p=0.003). In addition, there was a statistically significant difference between groups in terms of N-terminal Pro-brain Natriuretic Peptide (NT-proBNP levels, p=0.008). Discussion. We compared diabetic and nondiabetic end-stage chronic kidney disease patients who were not in renal replacement therapy yet. We found more volume overload and extracellular fluid volume in the diabetic group.

The determination of cardiac peptides at rest and during exercise stress testing (ET) represents a useful tool for the diagnosis of heart failure patients, but their usefulness in isolated LV diastolic dysfunction was less studied until now.\r\nAim. The aim of this study is to compare the effect of ET upon cardiac peptides in patients with left ventricular systolic and diastolic dysfunction.\r\nMethods. There were studied 101 heart failure patients, 58 with systolic LV dysfunction (LVEF 37.8%) and 43 patients with isolated LV diastolic dysfunction, mainly with hypertension (31 cases). All patients were submitted to a symptom-limited ET on cycloergometer, blood samples being obtained before ET and at peak effort. The plasmatic levels of N terminal pro brain-type natriuretic peptide (NT-proBNP) were determined using ELISA method (n.v. <250 fmol/ml). The systolic and diastolic LV functions were determined by echo-Doppler, according to ESC guidelines.\r\nResults. The results showed that the rest NT-proBNP values were increased in patients with LV systolic dysfunction (640?220 fmol/ml) in comparison with diastolic dysfunction (419 ?120 fmol/ml), p<0.01. At peak effort NT-proBNP increased to 790?242 fmol/ml (23%) in patients with systolic dysfunction (p<0.04) and to 490.2?179 fmol/ml (17%) in patients with diastolic dysfunction (p= NS). There was a close relationship between rest and exercise NT-proBNP values in both systolic (r=0.99, p< 0.05) and diastolic (r=0.72) LV dysfunction. \r\nIn conclusion, in heart failure patients with both systolic and diastolic LV dysfunction, NT-proBNP is increased at rest and during exercise, the increase being significant for patients with LV systolic dysfunction, probably in relationship with more important hemodynamic abnormalities.

A study was performed on the basis of multiple-choice questionnaires applied to a lot of 96 pupils in the forms 9 to 11 at a high-school in the city of Suceava. The questionnaires of 96 de respondents were analysed ? 42 teenage boys (13 from the rural environment, 29 from the urban environment) and 54 teenage girls (19 from the rural environment and 35 from the urban environment). The objectives of the questions were: clarifying the relationships between the teenager and the social and family environment, affiliation to the reference group, knowledge and attitudes concerning the various aspects of sex life: the affective component, the start of sexual activity, notions about contraception and STD-s, the teenagers? attitude concerning the introduction of sex education in school. Most of the teenagers have an optimistic projection on the society?s permissive mentality concerning them and they enjoy a favourable family climate. Affiliation to the peer group, as a reference group, is based on fundamentally positive criteria and moral values and less based on professional interests. Love is perceived in an ideal manner, especially by teenage girls. The optimal age for becoming sexually active is declared as being 16-18 by most of the boys and 19-21 by most of the girls. The notions about contraception have a general character, and their practical application is more frequent with the boys than with the girls. The notions about sexually transmitted diseases, risk and prevention, are slightly better in boys than in girls. The main sources of information the teenagers have about their own sexuality are the media, more than the family and the educators. Although most of the teenagers agree with the need to have sex education in school, they could not offer solutions on the practical ways of delivering this education.

Objective. The existing studies involving omentin-1 have mainly focused on relationships with single cardiovascular risk factor. Whether omentin-1 is associated with the aggregation of cardiovascular risk factors has not been reported. We investigate the relationship between the serum omentin-1 level and aggregation of cardiovascular risk factors in adolescents. Subjects and Methods. A total of 741 young students, 11–16 years of age, were enrolled using a stratified cluster sampling method. The participants were given a questionnaire survey and underwent a physical examination. The aggregation of cardiovascular risk factors was defined as two or more cardiovascular risk factors occurring simultaneously in the same individual. Results. Partial correlation analysis suggested that serum omentin-1 level was significantly correlated with waist circumference (R=-0.086, P=0.019) and Body Mass Index (R=-0.096, P=0.009). Logistic regression analysis showed that as the serum omentin-1 level increased, the risk of aggregation of cardiovascular risk factors decreased. Cardiovascular risk factors which were most closely associated with a decrease in the serum omentin-1 level were obesity calculated by Body Mass Index (OR=0.988, P=0.043) and central obesity calculated by waist circumference (OR=0.993, P=0.012). Conclusions. The serum omentin-1 level in adolescents is inversely associated with the aggregation of cardiovascular risk factors. Waist circumference and Body Mass Index are factors most closely associated with a decrease in the serum omentin-1 level.